Impact of Exogenous Ketones on Sleep Disruption in Vulnerable Populations: Phase 2 Study (KETO-SLEEP 2)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Apnea Hypopnea Index (AHI)
研究概览
简要总结
Obstructive Sleep Apnea (OSA) is a common medical disorder that is associated with reduced quality of life and higher risk of cardiovascular disease. Treatments for OSA and limited and not well tolerated. The investigator's lab has shown that a low carbohydrate, high fat ketogenic diet (KD) can reduce OSA severity. Since it can be challenging to adhere to a ketogenic diet, the investigators propose that ingesting exogenous ketones can be an alternative method to improve OSA. Specifically the investigators will examine the effect of taking a commercially available product (Ketone-IQ) at bedtime on overnight ketones and sleep quality. The investigators will also examine the effect of Ketone-IQ on sleep apnea severity, compared to placebo.
This project will examine the the preliminary efficacy of ingesting exogenous ketones before sleep on sleep apnea.
详细描述
Sleep is a vulnerable period during which blunted respiratory drive and low airway muscle tone can cause dangerous breathing disorders. Obstructive sleep apnea (OSA) describes the intermittent collapse of the upper airway that induces O2 desaturations and arousals from sleep, placing patients at risk for cardiovascular disease, stroke, and death. In some obese patients, sleep causes carbon dioxide (CO2) accumulation progressing to daytime hypercapnia, a condition called obesity hypoventilation syndrome (OHS). Continuous positive airway pressure (CPAP) treats OSA and OHS, but is poorly tolerated, and may not fully correct sleep dysfunction.
Changes in metabolism may help to control OSA or OHS. The investigators recently published results from the Ketogenic Diet for OHS clinical trial (KETOHS, NCT04108819) showing that a 2-week ketogenic diet (high fat, low carbohydrate) for patients with OSA and OHS lowered reduced CO2, serum bicarbonate (HCO3), respiratory quotient, nocturnal hypoxemia(2). KD also significantly improved OSA. After participants resumed prior diet, CO2 returned to baseline. The mechanisms by which KD improves sleep in this population could be related to reduced CO2 production (through fat oxidation), lowering of body weight, or direct effects of ketone bodies on sleep and breathing.
It is difficult to adhere long-term to KD, and there are multiple effects of this diet that make it challenging to understand mechanistic impacts on respiration. The investigators hypothesize that increasing ketone levels in the body, without having to adhere to a ketogenic diet, may be another method to improve breathing during sleep. Indeed, some drugs affecting acid-base status (e.g. acetazolamide or sulthiame) improve OSA, presumably through increasing and stabilizing respiratory drive. In this pilot study, the investigators will examine the pharmacokinetics, tolerability, and impacts of ingesting exogenous ketones (which are commercially available products) on sleep and breathing.
The specific ketone product to be tested for its impact on sleep and breathing is 1,3 butanediol (1,3BD) in a commercially available formulation called "Ketone IQ". 1,3BD is converted by liver metabolism into the ketone body beta-hydroxybutyrate (BHB) and has been utilized in multiple studies.
This project will be conducted in two studies, KETO-SLEEP 1 (KS1), and KETO-SLEEP 2 (KS2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-65 years old with a BMI of 18 - 35 kg/m2
- •History of moderate-severe OSA as defined by AHI >15 events/hr (American Academy of Sleep Medicine criteria),
- •Adherent to CPAP (objectively determined via device download over last 30 days) using CPAP at least 70% of days for >=4 hours.
- •CPAP pressure ≤10 cm water (H2O) (based on prescribed CPAP pressure, or median pressure on an auto-titrating CPAP device).
排除标准
- •No concomitant sleep disorder (such as insomnia, restless leg syndrome, narcolepsy, idiopathic hypersomnia)
- •No current daytime respiratory impairment such as uncontrolled asthma, or uncontrolled chronic obstructive pulmonary disease (COPD), pneumonia, interstitial lung disease.
- •No use of supplemental oxygen.
- •Currently on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones
- •Pregnancy or breastfeeding
- •Alcohol consumption of > 10 standard drinks per week
- •Use of nightly medications that affect breathing (e.g. opiates, acetazolamide)
- •Use of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. For example, Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro)
研究组 & 干预措施
Ketone-IQ first
This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Ketone-IQ first, then placebo.
干预措施: Ketone-IQ (Dietary Supplement)
Ketone-IQ first
This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Ketone-IQ first, then placebo.
干预措施: Placebo (Dietary Supplement)
Placebo first
This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Placebo first, then Ketone-IQ.
干预措施: Ketone-IQ (Dietary Supplement)
Placebo first
This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Placebo first, then Ketone-IQ.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Apnea Hypopnea Index (AHI)
时间窗: 2 nights Ketone-IQ, 2 nights Placebo
Sleep studies will be performed using NOX T3 devices at home. The device will be worn for 2 consecutive nights during each intervention (Ketone IQ, Placebo); 4 nights total (2 nights Ketone-IQ, 2 nights Placebo). Apnea hypopnea index (AHI); mean number of apnoeas and hypopnoeas per hour of sleep will be calculated from NOX T3 data.
次要结局
- Gastrointestinal Symptoms Questionnaire(2 mornings after Ketone-IQ, 2 mornings after Placebo)
- Sleep-Related Impairment (SRI) as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS-SRI 8a)(2 mornings after Ketone-IQ, 2 mornings after Placebo)
- Sleep Disturbance (SD) as assessed by the PROMIS SD(2 mornings after Ketone-IQ, 2 mornings after Placebo)
- Stanford Sleepiness Scale (SSS)(2 mornings after Ketone-IQ, 2 mornings after Placebo)
- Oxygen Saturation Level(2 nights on Ketone IQ, 2 nights on placebo)
- Nadir Oxygen Level(2 nights on Ketone IQ, 2 nights on placebo)
- Oxygen Desaturation Index(2 nights on Ketone IQ, 2 nights on placebo)